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논문 기본 정보

자료유형
학술저널
저자정보
(강원대학교) (국립암센터) (울산과학기술원) (한국생명공학연구원) (피씨엘주식회사) (강원대학교) (강원대학교) ((재)스크립스코리아항체연구원) (강원대학교)
저널정보
한국분자세포생물학회 Molecules and Cells Molecules and Cells 제40권 제9호
발행연도
수록면
655 - 666 (12page)
DOI
10.14348/molcells.2017.0106

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초록· 키워드

We constructed a large naive human Fab library (3 ? 1010 colonies) from the lymphocytes of 809 human donors, assessed available diversities of the heavy-chain variable (VH) and κ light-chain variable (VK) domain repertoires, and validated the library by selecting Fabs against 10 therapeutically relevant antigens by phage display. We obtained a database of unique 7,373 VH and 41,804 VK sequences by 454 py-rosequencing, and analyzed the repertoires. The distribution of VH and VK subfamilies and germline genes in our antibody repertoires slightly differed from those in earlier published natural antibody libraries. The frequency of somatic hypermutations (SHMs) in heavy-chain complementarity determining region (HCDR)1 and HCDR2 are higher compared with the natural IgM repertoire. Analysis of position-specific SHMs in CDRs indicates that asparagine, threonine, arginine, aspartate and phenylalanine are the most frequent non-germline residues on the antibody-antigen interface and are converted mostly from the germline residues, which are highly represented in germline SHM hotspots. The amino acid composition and length-dependent changes in amino acid frequencies of HCDR3 are similar to those in previous reports, except that frequencies of aspartate and phenylalanine are a little higher in our repertoire. Taken together, the results show that this antibody library shares common features of natural antibody repertoires and also has unique features. The antibody library will be useful in the generation of human antibodies against diverse antigens, and the information about the diversity of natural antibody repertoires will be valuable in the future design of synthetic human antibody libraries with high functional diversity.
#diversity #human monoclonal antibody #naive antibody library #phage display #somatic hypermutation
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